Tetracyclines are well known broad spectrum antibiotics. Recently antibiotic tetracyclines have also been discovered to inhibit the activity of collagen destructive enzymes, e.g. mammalian collagenase, macrophage elastase and bacterial collagenases. For example, tetracyclines have recently been found to be useful in the treatment of periodontal diseases, severe progressive adult periodontitis and localized juvenile periodontitis. Antibiotic tetracyclines are also useful in the treatment of non-infected corneal ulcers, in the treatment of pathologically excessive bone resorption, in the treatment of joint destruction involved with rheumatoid arthritis and generally in the treatment of those diseases characterized by excessive collagen destruction.
In vitro tests have shown that antibiotic tetracyclines
(1) inhibit leukocyte and chondrocyte collagenase activity;
(2) reduce bone resorption in organ culture induced by either parathyroid hormone, bacterial endotoxin or prostaglandin E.sub.2 ; and
(3) reduce macrophage collagenase and elastase activity in cell culture.
Also, in in vivo tests the antibiotic tetracycline, minocycline, in the treatment of diabetic rat was found to
(a) reduce pathologically excessive collagenase activity in gingiva and skin;
(b) reduce pathological skin collagen resorption, and
(3) reduce pathologically excessive alveolar bone loss.
Moreover, clinically, the antibiotic tetracyclines (Minocin, Achromycin and Vibramycin) at regular and low-dose levels were found to reduce collagenase activity in human periodontal pockets and regular dose levels of tetracycline brought about the healing of refractory non-infected corneal ulcers in humans, lesions which are believed to be mediated by mammalian collagenase.
However, although the commercially available antibiotic tetracyclines are effective as anti-collagenolytic agents, long term use, either continuously or episodically, e.g. two weeks on-three months off-two weeks on-three months off, is subject to the usual complications of long term antibiotic usage, such as intestinal disburbance, overgrowth of yeast and fungi, the development of antibiotic resistant bacteria, etc.
Accordingly, it is an object of this invention to provide compositions and therapies based on tetracyclines, and particularly the utilization of tetracyclines which have anti-collagenolytic activity in the treatment of diseases or conditions characterized by excessive collagon destruction, without at the same time giving rise to the usual complications involved with long term antibiotic use.
It is another object of this invention to provide tetracycline-containing compositions and the use of such commpositions as anti-collagenase agents while at the same time providing novel compositions and applications of such compositions in the treatment of various diseases and conditions characterized by excessive collagen destruction.
It is a special object or aspect of this invention to provide tetracycline compositions having improved properties, such as animal feed compositions containing tetracyclines which are effective when supplied or administered to animals not only as anti-collagenolytic agents but which also provide improved animal nutrition.
Current usage of the antibiotic tetracycline as an additive to animal feed for promoting improved feed conversion and weight gain has been found to have the adverse effect of producing the overgrowth of resistant organisms which are presently considered to be hazardous to human health. By the practice of this invention this adverse effect is eliminated while at the same time animal weight gain is promoted.